CA2560432A1 - Pseudo-thermosetting neutralized chitosan composition forming a hydrogel and a process for producing the same - Google Patents
Pseudo-thermosetting neutralized chitosan composition forming a hydrogel and a process for producing the same Download PDFInfo
- Publication number
- CA2560432A1 CA2560432A1 CA002560432A CA2560432A CA2560432A1 CA 2560432 A1 CA2560432 A1 CA 2560432A1 CA 002560432 A CA002560432 A CA 002560432A CA 2560432 A CA2560432 A CA 2560432A CA 2560432 A1 CA2560432 A1 CA 2560432A1
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- Prior art keywords
- chitosan
- pseudo
- deacetylation degree
- solution
- cooled
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Materials For Medical Uses (AREA)
Abstract
The composition disclosed is a pseudo-thermosetting neutralized chitosan composition, neutralized with an hydroxylated base, forming a phosphate-free transparent hydrogel at a temperature higher than 5~C. Said composition contains a homogeneously reacetylated chitosan derived from a chitosan having a deacetylation degree of 80 - 90 %, having a molecular weight of not smaller than 200 kDa and a deacetylation degree of 30 - 60 %, and may further contain a diol. Said composition may be used as a drug delivery system.
Claims (19)
1. A pseudo-thermosetting neutralized chitosan composition, which comprises 0.1 to 2.0 wt/v %, based on the total composition, of a homogeneously reacetylated chitosan derived from a chitosan having a deacetylation degree of 80 - 90 %, having a molecular weight of not smaller than 200 kDa and a deacetylation degree of 30 - 60 %, neutralized with an hydroxylated base, wherein said composition forms a phosphate-free transparent hydrogel at a temperature higher than 5°C.
2. The pseudo-thermosetting neutralized chitosan composition according to claim 1, comprising 0.5 to 1 wt/v %, based on the total composition, of said homogeneously reacetylated chitosan.
3. The pseudo-thermosetting neutralized chitosan composition according to claim 1 or 2, wherein the deacetylation degree of said homogeneously reacetylated chitosan is 45 to 55 %.
4. The pseudo-thermosetting neutralized chitosan composition according to anyone of claims 1 to 3, wherein the molecular weight of said homogeneously reacetylated chitosan is not smaller than 600 kDa.
5. The pseudo-thermosetting neutralized chitosan composition according to anyone of claims 1 to 4, further comprising a diol having a distance of at least 4.7 .ANG.
between its hydroxyl groups.
between its hydroxyl groups.
6. The pseudo-thermosetting neutralized chitosan composition according to claim 5, wherein said diol is 1,3-propanediol.
7. A process for producing a homogeneously reacetylated chitosan having a molecular weight of not smaller than 200 kDa and a deacetylation degree of 30 - 60 % which comprises the steps of:
a) filtrating a chitosan having a molecular weight of not smaller than 200 kDa and a deacetylation degree of 80 to 90 % dissolved in an acidic medium to eliminate insoluble particles;
b) precipitating chitosan contained in the filtrated acidic solution obtained in step a) to obtain chitosan free of insoluble particles;
c) preparing a cooled acidic solution of the chitosan free of insoluble particles obtained in step b) at a temperature lower than 5°C to obtain a cooled acidic solution of chitosan free of insoluble particles;
d) preparing a cooled acetic anhydride solution containing a predetermined amount of acetic anhydride in methanol at a temperature lower than 5°C;
e) reacetylating chitosan by adding dropwise, under homogeneous conditions, the cooled acetic anhydride solution of step d) to the cooled solution of chitosan prepared in step c) to provide a crude homogeneously reacetylated chitosan having a deacetylation degree of 30 - 60 %;
f) treating said crude chitosan obtained in step e) to eliminate salts produced during reacetylation and insoluble particles of chitosan to obtain a homogeneously reacetylated chitosan having a deacetylation degree of 30 - 60 %.
a) filtrating a chitosan having a molecular weight of not smaller than 200 kDa and a deacetylation degree of 80 to 90 % dissolved in an acidic medium to eliminate insoluble particles;
b) precipitating chitosan contained in the filtrated acidic solution obtained in step a) to obtain chitosan free of insoluble particles;
c) preparing a cooled acidic solution of the chitosan free of insoluble particles obtained in step b) at a temperature lower than 5°C to obtain a cooled acidic solution of chitosan free of insoluble particles;
d) preparing a cooled acetic anhydride solution containing a predetermined amount of acetic anhydride in methanol at a temperature lower than 5°C;
e) reacetylating chitosan by adding dropwise, under homogeneous conditions, the cooled acetic anhydride solution of step d) to the cooled solution of chitosan prepared in step c) to provide a crude homogeneously reacetylated chitosan having a deacetylation degree of 30 - 60 %;
f) treating said crude chitosan obtained in step e) to eliminate salts produced during reacetylation and insoluble particles of chitosan to obtain a homogeneously reacetylated chitosan having a deacetylation degree of 30 - 60 %.
8. The process according to claim 7, wherein the treating step f) includes the steps of:
f-1) dialyzing chitosan obtained in step e) to eliminate salts produced during reacetylation in order to obtain a homogeneously reacetylated chitosan solution;
f-2) filtrating the chitosan solution obtained in step f-1) to eliminate insoluble particles of chitosan;
f-3) precipitating chitosan contained in the filtrated solution obtained in step f-2) and then drying chitosan to obtain a homogeneously reacetylated chitosan having a deacetylation degree of 30 - 60 %.
f-1) dialyzing chitosan obtained in step e) to eliminate salts produced during reacetylation in order to obtain a homogeneously reacetylated chitosan solution;
f-2) filtrating the chitosan solution obtained in step f-1) to eliminate insoluble particles of chitosan;
f-3) precipitating chitosan contained in the filtrated solution obtained in step f-2) and then drying chitosan to obtain a homogeneously reacetylated chitosan having a deacetylation degree of 30 - 60 %.
9. The process according to claim 8, wherein the precipitating step f-3) includes addition of a mixture of NH4OH/methanol.
10. A homogeneously reacetylated chitosan having a molecular weight of not smaller than 200 kDa and a deacetylation degree of 30 - 60 % obtained by the process as claimed in anyone of claims 7-9 for use in the preparation of a pseudo-thermosetting neutralized chitosan composition forming a phosphate-free transparent hydrogel at a temperature higher than 5°C.
11. A process for producing a pseudo-thermosetting neutralized chitosan composition forming a phosphate-free, transparent hydrogel at a temperature higher than 5°C, which comprises the steps of:
g) solubilizing a homogeneously reacetylated chitosan derived from a chitosan having a deacetylation degree of 80 - 90 %, having a molecular weight of not smaller than 200 kDa and a deacetylation degree of 30 - 60 %, in an aqueous HCI medium and cooling said acidic chitosan solution at a temperature lower than 5°C;
h) neutralizing the cooled chitosan solution obtained in step g) by adding an aqueous hydroxylated base previously cooled at a temperature lower than 5°C to the cooled chitosan solution until the cooled solution of chitosan exhibits a pH of 6.8-7.2;
i) optionally, increasing the temperature of the neutral cooled solution of chitosan obtained in step h) at a temperature higher than 5°C in order to induce pseudo-thermogelation.
g) solubilizing a homogeneously reacetylated chitosan derived from a chitosan having a deacetylation degree of 80 - 90 %, having a molecular weight of not smaller than 200 kDa and a deacetylation degree of 30 - 60 %, in an aqueous HCI medium and cooling said acidic chitosan solution at a temperature lower than 5°C;
h) neutralizing the cooled chitosan solution obtained in step g) by adding an aqueous hydroxylated base previously cooled at a temperature lower than 5°C to the cooled chitosan solution until the cooled solution of chitosan exhibits a pH of 6.8-7.2;
i) optionally, increasing the temperature of the neutral cooled solution of chitosan obtained in step h) at a temperature higher than 5°C in order to induce pseudo-thermogelation.
12. The process according to claim 11, further comprising a step of sterilizing chitosan before the step g) of solubilization.
13. The process according to claim 11 or 12, wherein in step h), the hydroxylated base is NaOH.
14. The process according to anyone of claims 11 to 13, further comprising the step of adding an appropriate amount of a diol having a distance of at least 4.7 .ANG. between the hydroxyl groups before, during or after the solubilization step g), or before, during or after the neutralization step h) to increase the consistency of the hydrogel to the required degree of consistency of the hydrogel.
15. The process according to claim 14, wherein the diol is 1,3-propanediol.
16. The process according to anyone of claims 11 to 15, wherein the homogeneously reacetylated chitosan solubilized in step g) is obtained by the process according to claims 7-9.
17. A phosphate-free transparent pseudo-thermosetting chitosan hydrogel obtained by the process as claimed in anyone of claims 11 to 16.
18. A use of a homogeneously reacetylated chitosan having a deacetylation degree of 30 - 60 % and a molecular weight of not smaller than 200 kDa obtained by the process as claimed in anyone of claims 7 to 10, for the preparation of a phosphate-free, transparent, pseudo-thermosetting chitosan hydrogel.
19. A use of a pseudo-thermosetting neutralized chitosan composition as claimed in anyone of claims 1-6, as a drug delivery system.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2004/002988 WO2005097871A1 (en) | 2004-03-22 | 2004-03-22 | Pseudo-thermosetting neutralized chitosan composition forming a hydrogel and a process for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2560432A1 true CA2560432A1 (en) | 2005-10-20 |
| CA2560432C CA2560432C (en) | 2012-10-09 |
Family
ID=34957126
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2560432A Expired - Fee Related CA2560432C (en) | 2004-03-22 | 2004-03-22 | Pseudo-thermosetting neutralized chitosan composition forming a hydrogel and a process for producing the same |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US8835514B2 (en) |
| EP (1) | EP1730216A1 (en) |
| JP (1) | JP5083967B2 (en) |
| CA (1) | CA2560432C (en) |
| WO (1) | WO2005097871A1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005097871A1 (en) * | 2004-03-22 | 2005-10-20 | Universite De Geneve | Pseudo-thermosetting neutralized chitosan composition forming a hydrogel and a process for producing the same |
| CN1330386C (en) * | 2005-12-07 | 2007-08-08 | 浙江大学 | Method for preparing injectable chitosan hydrogen for tissue engineering |
| CN100431624C (en) * | 2005-12-07 | 2008-11-12 | 浙江大学 | Method for preparing injectable polyletic acid micro-carrier/chitosan hydrogel composite scaffold |
| JP5474353B2 (en) * | 2005-12-23 | 2014-04-16 | ラボラトワール メディドム エス． エー． | Thermoplastic neutralized chitosan composition to form a hydrogel, lyophilizate, and method for producing them |
| US9034348B2 (en) | 2006-12-11 | 2015-05-19 | Chi2Gel Ltd. | Injectable chitosan mixtures forming hydrogels |
| JP2011511123A (en) * | 2008-01-31 | 2011-04-07 | ザ プロクター アンド ギャンブル カンパニー | Acetylation of chitosan |
| AU2009258885A1 (en) * | 2008-06-11 | 2009-12-17 | Chi2Gel Ltd. | Injectable hydrogel forming chitosan mixtures |
| US9547011B2 (en) * | 2013-03-14 | 2017-01-17 | Tricol Biomedical, Inc. | Biocompatible and bioabsorbable derivatized chitosan compositions |
| FR3016882A1 (en) | 2014-01-30 | 2015-07-31 | Sofradim Production | PROCESS FOR THE PREPARATION OF HIGH-DEGREE ACETYLATION CHITOSAN |
| CN114805859B (en) * | 2022-06-16 | 2023-08-29 | 安阳师范学院 | A kind of preparation method of heat setting chitosan hydrogel |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4659700A (en) * | 1984-03-02 | 1987-04-21 | Johnson & Johnson Products, Inc. | Chitosan-glycerol-water gel |
| JPS624702A (en) | 1985-06-28 | 1987-01-10 | Lion Corp | Production of water-soluble acrylated chitosan |
| JPH0790005A (en) * | 1993-09-24 | 1995-04-04 | Daiichi Seimo Kk | Production of water-soluble chitosan |
| JP3118423B2 (en) * | 1996-08-30 | 2000-12-18 | ツヤック株式会社 | Method for producing water-soluble partially acetylated chitosan solution |
| CA2212300A1 (en) | 1997-08-04 | 1999-02-04 | Abdellatif Chenite | In vitro or in vivo gelfying chitosan and therapeutic uses thereof |
| FR2822842B1 (en) * | 2001-03-30 | 2004-11-19 | Genevrier Lab | PROCESS FOR THE PREPARATION OF A CARTILAGINOUS NEO-TISSUE |
| NO20015986D0 (en) * | 2001-08-02 | 2001-12-06 | Einar J Mustaparta | The product chitosan, as well as the method of manufacture and use of chitosan |
| FR2836044A1 (en) * | 2002-02-15 | 2003-08-22 | Octaris | COMPOSITION FOR REPAIR AND SKIN HEALING EXCLUSIVELY INCLUDING A TRUE PHYSICAL HYDROGEL OF CHITOSAN |
| WO2005097871A1 (en) * | 2004-03-22 | 2005-10-20 | Universite De Geneve | Pseudo-thermosetting neutralized chitosan composition forming a hydrogel and a process for producing the same |
| JP2007090005A (en) | 2005-09-27 | 2007-04-12 | Oputisu Engineering Company:Kk | Instrument for training abdominal muscle or the like |
| JP2010072502A (en) | 2008-09-22 | 2010-04-02 | Hitachi Displays Ltd | Liquid crystal display device |
-
2004
- 2004-03-22 WO PCT/EP2004/002988 patent/WO2005097871A1/en active Application Filing
- 2004-03-22 EP EP04722250A patent/EP1730216A1/en not_active Withdrawn
- 2004-03-22 US US10/593,678 patent/US8835514B2/en not_active Expired - Fee Related
- 2004-03-22 JP JP2007504258A patent/JP5083967B2/en not_active Expired - Fee Related
- 2004-03-22 CA CA2560432A patent/CA2560432C/en not_active Expired - Fee Related
-
2009
- 2009-12-29 US US12/654,700 patent/US8507563B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1730216A1 (en) | 2006-12-13 |
| US8507563B2 (en) | 2013-08-13 |
| JP2007529559A (en) | 2007-10-25 |
| US20100113618A1 (en) | 2010-05-06 |
| WO2005097871A1 (en) | 2005-10-20 |
| JP5083967B2 (en) | 2012-11-28 |
| US8835514B2 (en) | 2014-09-16 |
| CA2560432C (en) | 2012-10-09 |
| US20070141142A1 (en) | 2007-06-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20170322 |